Regulation of actin catch-slip bonds with a RhoA-formin module
| Autor: | Jizhong Lou, Larry V. McIntire, Peter A. Rubenstein, Kuo-Kuang Wen, Shoichiro Ono, Cho-yin Lee, Melissa McKane, Shu Chien, Suzanne G. Eskin, Cheng Zhu |
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| Rok vydání: | 2016 |
| Předmět: |
Models
Molecular 0301 basic medicine RHOA 1.1 Normal biological development and functioning Arp2/3 complex macromolecular substances Molecular Dynamics Simulation Article 03 medical and health sciences Actin remodeling of neurons Underpinning research Models Animals Actin-binding protein Binding Sites Multidisciplinary biology Lysine Microfilament Proteins Molecular Actin remodeling Actin cytoskeleton Actins Cell biology Other Physical Sciences 030104 developmental biology Amino Acid Substitution Gene Expression Regulation Generic Health Relevance Formins biology.protein Biochemistry and Cell Biology MDia1 rhoA GTP-Binding Protein Protein Binding |
| Zdroj: | Scientific reports, vol 6, iss 1 Scientific Reports Lee, C-Y; Lou, J; Wen, K-K; McKane, M; Eskin, SG; Rubenstein, PA; et al.(2016). Regulation of actin catch-slip bonds with a RhoA-formin module. SCIENTIFIC REPORTS, 6. doi: 10.1038/srep35058. UC San Diego: Retrieved from: http://www.escholarship.org/uc/item/01j7b0m2 |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep35058 |
| Popis: | The dynamic turnover of the actin cytoskeleton is regulated cooperatively by force and biochemical signaling. We previously demonstrated that actin depolymerization under force is governed by catch-slip bonds mediated by force-induced K113:E195 salt-bridges. Yet, the biochemical regulation as well as the functional significance of actin catch bonds has not been elucidated. Using AFM force-clamp experiments, we show that formin controlled by RhoA switches the actin catch-slip bonds to slip-only bonds. SMD simulations reveal that the force does not induce the K113:E195 interaction when formin binds to actin K118 and E117 residues located at the helical segment extending to K113. Actin catch-slip bonds are suppressed by single residue replacements K113E and E195K that interrupt the force-induced K113:E195 interaction; and this suppression is rescued by a K113E/E195K double mutant (E/K) restoring the interaction in the opposite orientation. These results support the biological significance of actin catch bonds, as they corroborate reported observations that RhoA and formin switch force-induced actin cytoskeleton alignment and that either K113E or E195K induces yeast cell growth defects rescued by E/K. Our study demonstrates how the mechano-regulation of actin dynamics is modulated by biochemical signaling molecules, and suggests that actin catch bonds may be important in cell functions. |
| Databáze: | OpenAIRE |
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